Pericyte plasticity and cerebrovascular health

Pericytes are a beautiful cell type to study. They come in a variety of shapes and sizes. The most elegant forms drape along the capillary bed like vines covering an old tree. While their cell bodies are small, their long processes reach outward to contact the majority of capillary bed (see images). These “vines” are important for cerebrovascular health. Studies have shown that reducing the number of pericytes or their coverage of the underlying endothelium leads to problems, including blood-brain barrier compromise, abnormal vascular structure, and impaired blood flow regulation. Pericytes are also uniquely vulnerable to brain disease and are lost in great numbers during Alzheimer’s disease, vascular dementia, and stroke. Therefore, understanding how pericytes interact with the endothelium may lead to approaches to improve cerebrovascular health in these diseases.

In our recent study, Ph.D. student Andrée-Anne Berthiaume asked the question of whether pericyte processes were dynamic in the intact brain. Structural plasticity might indicate that pericytes could regrow in the face of injury/disease. Indeed, after tracking fluorescently-tagged pericytes for days to weeks using two-photon imaging, Andrée-Anne saw evidence of motility at the distal tips of pericytes processes. However, these changes were miniscule. She hypothesized that pericytes were territorial, negotiating their territories with neighboring pericytes that restricted their growth. To test this idea, she used precise lasers to ablate a pericyte and found that this led to a robust growth of neighboring cell processes to cover the exposed vasculature. Moreover, without pericyte contact, capillaries dilated beyond the normal range suggesting altered blood flow control.

These data provided evidence for an intrinsic program that allows pericytes to compensate for the loss of their neighbors. What are the mechanisms underlying this reparative function? What happens to blood vessels when we block it? Does pericyte plasticity diminish as we age? These are some of the exciting questions that we are focusing on next.